Construction and validation of a perioperative concomitant lower extremity deep vein thrombosis line graph model in patients with aneurysmal subarachnoid hemorrhage.

Background: To develop and validate a nomogram for predicting the probability of deep venous thrombosis (DVT) in patients with aneurysmal subarachnoid hemorrhage (aSAH) during the perioperative period, using clinical features and readily available biochemical parameters. Methods: The least absolute shrinkage and selection operator (LASSO) regression technique was employed for data dimensionality reduction and selection of predictive factors. A multivariable logistic regression analysis was conducted to establish a predictive model and nomogram for post-aSAH DVT. The discriminative ability of the model was determined by calculating the area under the curve (AUC). Results: A total of 358 aSAH patients were included in the study, with an overall incidence of DVT of 20.9%. LASSO regression identified four variables, including age, modified Fisher grade, total length of hospital stay, and anticoagulation therapy, as highly predictive factors for post-aSAH DVT. The patients were randomly divided into a modeling group and a validation group in a 6:4 ratio to construct the nomogram. The AUCs of the modeling and validation groups were 0.8511 (95% CI, 0.7922-0.9099) and 0.8633 (95% CI, 0.7968-0.9298), respectively. Conclusions: The developed nomogram exhibits good accuracy, discriminative ability, and clinical utility in predicting DVT, aiding clinicians in identifying high-risk individuals and implementing appropriate preventive and treatment measures.

Rasd1 is involved in white matter injury through neuron-oligodendrocyte communication after subarachnoid hemorrhage.

AIMS: Rasd1 has been reported to be correlated with neurotoxicity, metabolism, and rhythm, but its effect in case of subarachnoid hemorrhage (SAH) remained unclear. White matter injury (WMI) and ferroptosis participate in the early brain injury (EBI) after SAH. In this work, we have investigated whether Rasd1 can cause ferroptosis and contribute to SAH-induced WMI. METHODS: Lentivirus for Rasd1 knockdown/overexpression was administrated by intracerebroventricular (i.c.v) injection at 7 days before SAH induction. SAH grade, brain water content, short- and long-term neurobehavior, Western blot, real-time PCR, ELISA, biochemical estimation, immunofluorescence, diffusion tensor imaging (DTI), and transmission electron microscopy (TEM) were systematically performed. Additionally, genipin, a selective uncoupling protein 2(UCP2) inhibitor, was used in primary neuron and oligodendrocyte co-cultures for further in vitro mechanistic studies. RESULTS: Rasd1 knockdown has improved the neurobehavior, glia polarization, oxidative stress, neuroinflammation, ferroptosis, and demyelination. Conversely, Rasd1 overexpression aggravated these changes by elevating the levels of reactive oxygen species (ROS), inflammatory cytokines, MDA, free iron, and NCOA4, as well as contributing to the decrease of the levels of UCP2, GPX4, ferritin, and GSH mechanistically. According to the in vitro study, Rasd1 can induce oligodendrocyte ferroptosis through inhibiting UCP2, increasing reactive oxygen species (ROS), and activating NCOA4-mediated ferritinophagy. CONCLUSIONS: It can be concluded that Rasd1 exerts a modulated role in oligodendrocytes ferroptosis in WMI following SAH.

Establishment and multicenter external validation of a risk prediction model for de novo intracranial aneurysms based on a systematic review and meta-analysis of 19 cohorts.

OBJECTIVE: A de novo intracranial aneurysm (IA) is a second, new IA that develops in patients with IAs distant from where the initial IA was detected. This study aimed to identify risk factors for de novo IA formation and establish and externally validate a multicenter risk prediction model for de novo IAs. METHODS: A systematic review and meta-analysis of existing de novo IA cohorts was conducted to form the derivation cohort. The risk ratios and 95% CIs of each risk factor were calculated. In addition, risk scores included in the model were calculated based on the statistically significant risk factors with their weightings. Then the model was validated in a multicenter external cohort of Chinese patients, and receiver operating characteristic and calibration curves, decision curve analysis, and Kaplan-Meier curves were used to evaluate the model. RESULTS: Nineteen studies with 9351 patients, of whom 304 patients (3.25%) developed de novo IAs, were included in the derivation cohort. These patients developed de novo IAs at 2.5-18.5 years during a total follow-up of 3.3-18.8 years. The statistically significant risk factors were age < 60 years, female sex, smoking history, family history of IAs, multiple IAs at initial diagnosis, and initial IAs in the middle cerebral artery, with risk scores of 4, 5, 2, 6, 3, and 3, respectively. Then, a multicenter external cohort comprising 776 patients, of whom 45 patients (5.80%) developed de novo IAs, was included in the validation cohort. De novo IAs formed in these patients at a mean of 5.25 years during a mean follow-up of 6.19 years. The area under the curve of the model was 0.804, with a sensitivity of 0.667 and specificity of 0.900, at a cutoff value of 13. The calibration curve, decision curve analysis, and Kaplan-Meier curves also indicated good performance of the model. CONCLUSIONS: This prediction model is a convenient and intuitive tool for identifying high-risk patients with de novo IAs. Reasonable use of the model can not only aid in clinical decision-making but also play a positive role in the prevention of aneurysmal subarachnoid hemorrhage to a certain extent.

Willis covered stent treatment for internal carotid artery pseudoaneurysm: A meta-analysis of efficacy and safety.

Background: Pseudoaneurysm (PSA) of internal carotid artery is a rare but severe cerebrovascular disease and difficult to repair surgically. A novel medical device called Willis covered stent (WCS) has been created especially for the treatment of complex cerebrovascular diseases. However, the efficacy and safety of WCS therapy for PSA are still debatable. Additional substantial proof is needed. Methods: To find research pertaining to WCS treatment for PSA, a systematic review of literature was conducted in the Medline, Embase, Web of Science, CNKI, Wanfang, and CBM databases. The results comprising the data of intraoperative situation, postoperative situation, and follow-up were then included in a meta-analysis. Results: The criteria were met by 11 noncomparative studies with 152 patients and 157 PSAs. Technical success rate was nearly 100 % (>0.999 (95 % confidence interval (CI), 0.958, 1.000)), complete occlusion rate was 97.8 % (95 % CI, 0.932, 1.000), and side branch occlusion rate was 0.5 % (95 % CI, 0.001, 0.045). The rates of acute in-stent thrombosis (<0.001 (95 % CI, 0.000, 0.013)) and hemorrhage (<0.001 (95 % CI, 0.000, 0.005)) were both less than 0.1 %. In postoperative situation, surgery-related mortality rate was less than 0.1 % (<0.001 (95 % CI, 0.000, 0.005)). The rates of recurrence (<0.001 (95 % CI, 0.000, 0.002)) and parent artery stenosis (<0.001 (95 % CI, 0.000, 0.008)) were both less than 0.1 %, while late in-stent stenosis occurred in 1.3 % (95 % CI, 0.000, 0.053) of patients. In the end, 98.5 % (95 % CI, 0.943, 1.000) of patients had a good outcome. Conclusion: The application of WCS could be effective and safe for PSAs. The findings of this study could serve as a reference for upcoming clinical trials.

A case report of oral sulfamethoxazole in the treatment of posttransplant Listeria monocytogenes meningitis.

Background: Renal transplant recipients are prone to Listeria monocytogenes (Lm) infection due to immunosuppressive therapies. Ampicillin or penicillin G is regarded as the first-line treatment of Lm meningitis. For patients with allergy to penicillin, convention to trimethoprim-sulfamethoxazole (TMP-SMX) iv should ideally be performed since TMP-SMX remarkable bactericidal activity. But there's still scarcity of reports indicating oral TMP-SMX regimen on Lm meningitis. Case Description: A 30-year-old male who received a renal transplant 4 months ago was admitted to the hospital with generalized pain and headache for 3 days accompanied by diarrhea and fever for 1 day. The patient had been treated with regular oral immunosuppressants post-transplantation. After admission, the patient poorly responded to cefoperazone sulbactam and progressed rapidly with increasing headache, persistent diarrhea, diplopia, and dyspnea and was subsequently transferred to the intensive care unit (ICU) for ventilatory support. Later, as Lm was detected successively in the patient's blood culture and cerebrospinal fluid culture, the patient was diagnosed with Lm infection. Due to the patient's allergy to penicillins, the TMP-SMX was selected for oral treatment, and the patient well tolerated to TMP-SMX oral regimen without significant adverse effects and recovered after 2 weeks. After discharge, follow-up has shown that the patient has generally remained in good condition with stable graft function to date. Conclusions: The case of our study demonstrated Lm infection post renal transplantation can be cured by oral TMP-SMX. Furthermore, the recent research and clinical progress of Lm microbiological characteristics, clinical manifestations, diagnosis, and treatment of listeriosis were summarized.

Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trials.

Background: Stroke, including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH), remains a leading cause of mortality globally. Different stroke subtypes have similar detrimental effects in multiple fields of health. Previous research has shown that metformin plays a neuroprotective role in experimental animal models of stroke; however, a preclinical quantitative analysis on the ability of metformin to treat stroke is still lacking. This meta-analysis evaluates the efficacy of metformin in improving stroke prognosis in rodent models of stroke. Methods: Relevant preclinical trials were retrieved from PubMed, EMBASE, and the Web of Science. The neurological score (NS), brain water content (BWC), infarct size, rotarod test, TUNEL, neuron quantity, microglia quantity, and p-AMPK levels were compared between a control group and a metformin group using the standardized mean difference (SMD) and corresponding confidence interval (CI). Quality was assessed with SYRCLE's risk of bias tool. Results: Fifteen articles published from 2010 to 2022 were included in the meta-analysis. The metformin group had statistically significant differences compared to the control group in the following aspects: NS (SMD -1.45; 95% CI -2.32, -0.58; p = 0.001), BWC (SMD -3.22; 95% CI -4.69, -1.76; p < 0.0001), infarct size (SMD -2.90; 95% CI -3.95, -1.85; p < 0.00001), rotarod test (SMD 2.55; 95% CI 1.87, 3.23; p < 0.00001), TUNEL (SMD -3.63; 95% CI -5.77, -1.48; p = 0.0009), neuron quantity (SMD 3.42; 95% CI 2.51, 4.34; p < 0.00001), microglia quantity (SMD -3.06; 95% CI -4.69, -1.44; p = 0.0002), and p-AMPK levels (SMD 2.92; 95% CI 2.02, 3.82; p < 0.00001). Furthermore, sensitivity analysis and stratified analysis were conducted for heterogeneous outcome indicators. Conclusion: Overall, metformin treatment improves severe outcomes triggered by stroke. Despite the limitations intrinsic to animal studies, this systematic review may provide a vital reference for future high-quality preclinical trials and clinical use.

Efficacy of Resveratrol in Experimental Subarachnoid Hemorrhage Animal Models: A Stratified Meta-Analysis.

Background: Subarachnoid hemorrhage (SAH) is a serious neurosurgical emergency with extremely high morbidity and mortality rates. Resveratrol (RES), a natural polyphenolic phytoalexin, is broadly presented in a wide variety of plants. Previous research had reasonably revealed its neuroprotective effects on experimental SAH animal models to some extent. But the results were more controversial. Therefore, we conducted a meta-analysis to evaluate the evidence on the effectiveness of RES in improving outcomes in SAH animal models. Methods: A systematic literature review was conducted in PubMed, EMBASE, and Web of Science databases to incorporate experimental control studies on the efficacy of RES on SAH models into our research. The standardized mean difference (SMD) was used to compare the brain water content (BWC) and neurological score (NS) between the treatment and control groups. Results: Overall, 16 articles published from 2014 to 2022 met the inclusion criteria. The meta-analysis of BWC showed a significant difference in favor of RES treatment (SMD: -1.026; 95% CI: -1.380, -0.672; p = 0.000) with significant heterogeneity (Q = 84.97; I2 = 60.0%; p = 0.000). Further stratified analysis was performed for methodological differences, especially dosage, time of treatments, and time-point of outcome assessment. The meta-analysis of NS showed a significant difference in favor of RES treatment (SMD: 1.342; 95% CI: 1.089, 1.595; p = 0.000) with low heterogeneity (Q = 25.58; I2 = 17.9%; p = 0.223). Conclusion: Generally, RES treatment showed an improvement in both pathological and behavioral outcomes in SAH animal models. The results of this study may provide a reference for preclinical and clinical studies in the future to some extent, with great significance for human health.

[Astragalus polysaccharide combined with cisplatin inhibits growth of recurrent tumor and down-regulats the expression of CD44, CD62P and osteopontin in tumor tissues in mice bearing Lewis lung cancer].

Objective To investigate the effects of Astragalus polysaccharide (APS) combined with cisplatin (DDP) on the pathological morphology of recurrent tumor and the expression of metastasis-related proteins CD44, CD62P and osteopontin (OPN) following Lewis lung carcinoma (LLC) surgery. Methods LLC cell suspension was injected subcutaneously into palmula of left hind limb of C57BL/6J mice as a tumor-supply group. The other 80 mice were randomized into 8 groups: model group, APS-treated groups at different concentrations of 50, 100 and 200 µg/mL, 6 mg/kg DDP-treated group, and 3 mg/kg DDP combined with 50, 100, 200 µg/mL APS-treated groups. The palmula tumor cells were collected from the tumor-supply group 10 days after LLC injection and then injected subcutaneously into all of the 80 mice to establish the recurrent and metastatic mouse models of lung cancer. Subsequently, corresponding different substances were administrated intraperitoneally in the different treated groups since the next day. After 15 days' administration, all the mice were sacrificed by cervical spine dislocation. Morphological characteristics were observed by H&E staining, and the protein expression of CD44, CD62P and OPN were measured by immunohistochemistry. Results Compared with the model group, the pathological changes of the recurrent tissues in each treatment group were alleviated to some extent, especially in the DDP combined with 200 µg/mL APS group; the expression of CD44, CD62P and OPN in each treatment group decreased, especially in the DDP group and DDP combined with 100 and 200 µg/mL APS-treated groups. Conclusion APS combined with DDP could significantly inhibit the growth and metastasis of Lewis lung cancer cells, which might be associated with the reduced expression of CD44, CD62P and OPN.